Enzyme-studies will involve measurements in human colo-rectal adenocarcinomas (HCRAC) of the levels of activity (and their inhibition) of enzymes required either (a) For the salvage of precursors, or (b) For the de novo-synthesis of uridine 5'-monophosphate (UMP), and (c) For the utilization of fluorinated pyrimidines that inhibit the biosynthesis of DNA (and toxicologically that of RNA). Compounds that synergize therapeutically with (c) While diminishing their toxicity for host-tissues, are being investigated. Studies of cells in culture permit extension of findings made with enzyme systems in vitro, and provide logical bases for chemotherapeutic studies, not only in immune-deprived mice bearing xenografts of HCRAC, but also in mice in which immunosuppression is maintained by treatment with anti-thymocyte sera. Among the latter, an important development, i.e., the development of ascitic HCRAC, as well as tumors that metastasize, is being applied to the development of new chemotherapeutic regimens. A new method of administration of a nucleoside that inhibits the salvage of uridine and cytidine, but does not enter either RNA or DNA, although it inhibits the formation of UMP, is under intensive study. Levels of normal and inhibitory nucleosides in tissues are being assessed with HPLC. Studies are being carried out of the mechanism of active transport into cells of nucleosides (and its inhibition). New studies of PALA, which apparently enters cells by diffusion, but now fails efficiently to inhibit the susceptible enzyme (in the de novo-pathway), will be conducted. An apparently new enzyme, other than uridine-cytidine kinase, which catalyzes the phosphorylation of many nucleosides, but possibly may be absent from HCRAC, is being studied intensively.